This invention relates to new substituted hexahydronaphthoxazines, pharmaceutical preparations containing such compounds as an active ingredient, and methods for using those compounds as pharmaceutical agents. More particularly, the invention relates to compounds having dopamine receptor agonist activity for therapeutic use in treating certain diseases of the central nervous system in mammals.
Compounds having dopaminergic activity have been the subject of extensive study in recent years, and a relatively large number of such compounds is known. The utility of L-DOPA in the symptomatic treatment of Parkinson's disease is well established and L-DOPA is in widespread clinical use. However, only a relatively small number of the other recognized dopaminergic agents have even been marketed. One of the major exceptions is Bromocriptine. Another promising compound has been Pergolide. However, most of the other compounds have not been commercialized because of a lack of pharmacological specificity; i.e., they have major and undesirable side effects.
One class of compounds that has excited a significant amount of activity in the field are the 9-oxaergolines. See, e.g., Anderson, et al., J. Med. Chem. 26, 363 (1983); Nedelec, et al., J. Med. Chem. 26, 522 (1983); Boissier, et al., Eur. J. Pharmacol., 87, 183 (1983); Martin, et al., Life Sci., 30, 1847 (1982).
The N-propyl-9-oxaergoline compound has been shown to be an extremely potent direct acting dopaminergic agonist, comparing favorably with pergolide.